Differentiating between tuberculous and non-tuberculous pleural effusions using the pleural fluid ratio of 10x adenosine deaminase/lactate dehydrogenase

Background: Adenosine deaminase (ADA) is a sensitive marker of tuberculous pleural effusion (TBPE). However, in pleural effusion (PE), the detection of ADA alone cannot be used to determine whether the increase in the ADA level is caused by the rising proportion of macrophages and lymphocytes in the cell components or by the increase in the total cell number. The diagnostic precision of ADA is probably restricted due to the false positive and negative results. Thus, we explored the clinical value of the ratio of PE ADA to lactate dehydrogenase (LDH) in differentiating between TBPE and non-TBPE. Methods: Patients hospitalized with PEs between January 2018 and December 2021 were retrospectively recruited for this study. We analyzed the values of ADA, LDH, and 10x ADA/LDH in the patients with TBPE and non-TBPE. We also determined the sensitivity, specificity, Youden index, and area under the curve for 10x ADA/LDH at different ADA levels and evaluated its diagnostic accuracy. Results: In total, 382 patients with PEs were included in the study. Among whom, 144 were diagnosed with TBPE, this supposes a "pre-test probability" >40%. It is quite high, 134 with malignant PEs, 19 with parapneumonic PEs, 43 with empyema, 24 with transudate PEs, and 18 with other types of PE of a known etiology. The ADA levels were positively correlated with the LDH levels in TBPE. LDH levels usually increase in response to cell damage or cell death. The 10x ADA/LDH level was significantly increased in the TBPE patients. In addition, the 10x ADA/LDH level increased as the ADA level increased in TBPE. To differentiate between TBPE and non-TBPE, the optimal cut-off value of 10x ADA/LDH at different ADA levels was assessed using receiver operating curves. At an ADA level >20 U/L, 10x ADA/LDH showed the best diagnostic performance, and had a specificity and sensitivity of 0.94 (95% CI: 0.84-0.98) and 0.95 (95% CI: 0.88-0.98), respectively. Conclusions: The 10x ADA/LDH dependent diagnostic index can be used to distinguish TBPE from non-TBPE and could be used to guide future clinical decisions.